The objective of this study was to evaluate the safety and efficacy of adalimumab 40 mg given every other week (eow) in subjects with active ankylosing spondylitis (AS) who have had an inadequate response to, or who are intolerant to, treatment with at least 1 nonsteroidal anti-inflammatory drug (NSAID) and who may have also failed treatment with at least 1 disease-modifying antirheumatic drug (DMARD).

Number of Responders With a Reduction of Signs and Symptoms of Ankylosing Spondylitis (AS) as Measured With ASAS International Working Group Response Criteria (ASAS 20). [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

ASAS 20 responders - improvement of >=20% and absolute improvement of >=10 units from Baseline in a visual analog scale (VAS) for >=3 of 4 domains; Patient's Global Assessment of disease activity VAS (0 [none]-100 [severe]), Total Back Pain VAS (0 [no pain]-100 [severe]), BASFI VAS (0 [easy]-100[impossible]); and Inflammation VAS (0 [none]-10 [very severe]) and absence of deterioration in the potential remaining domain, defined as a worsening of >=20% and a net worsening of >=10 units. Applied to each scale and not to an overall global scale.

Mean Change in the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) Compared Against a Historical Control Group (Outcomes in Ankylosing Spondylitis International Study [OASIS]) Using the ANCOVA Model Adjusting for Baseline mSASSS Score [ Time Frame: Week 104 ] [ Designated as safety issue: No ]

Radiographic progression was based on change in mSASSS scoring (comparison of the means) from double-blind Baseline visit to Week 104. The mSASSS is the sum of the lumbar and cervical spine score ( 0 [no change] to 72 [progression]), derived from scoring the anterior site of the lumbar spine (T12 to S1) and the cervical spine (C2 to T1) as either 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), 3 (bridging syndesmophyte), or N (vertebral body not evaluable). Data from NCT00195819 was compared with data from AS patients in OASIS.

ASAS 20 responders - improvement of >=20% and absolute improvement of >=10 units from Baseline in a visual analog scale (VAS) for >=3 of 4 domains; Patient's Global Assessment of disease activity VAS; (0[none]-100 [severe]), Total Back Pain VAS; (0 [no pain]-100 [severe]), BASFI VAS (0 [easy ]-100[impossible]); and Inflammation VAS (0 [none] to 10 [very severe]) and absence of deterioration in the potential remaining domain, defined as a worsening of >=20% and a net worsening of >=10 units. Applied to each scale and not to an overall global scale.

ASAS 50 responders - improvement of >=50% and absolute improvement of >=20 units from Baseline in a visual analog scale (VAS) for >=3 of 4 domains: Patient's Global Assessment of disease activity VAS (0 [none] to 100 [severe]); Total Back Pain VAS (0 [no pain] to 100 [severe]); BASFI VAS (0 [easy] to 100[impossible]); and Inflammation VAS (1 [none] to 10 [very severe]); and absence of deterioration in the potential remaining domain, defined as a worsening of >=20% and a net worsening of >=10 units. Applied to each scale and not to an overall global scale.

ASAS 70 responders - improvement of >=70% and absolute improvement of >=30 units from Baseline in a visual analog scale (VAS) for >=3 of 4 domains: Patient's Global Assessment of disease activity VAS (0 [none] to 100 [severe]), Total Back Pain VAS; (0 [no pain] - 100 [severe]), BASFI VAS (0 [easy] to 100[impossible]); and Inflammation VAS (1 [none] to 10 [very severe]); and absence of deterioration in the potential remaining domain, defined as defined as a worsening of >= 20% and a net worsening of >= 10 units. Applied to each scale and not to an overall global scale.

Evaluation of the effect of adalimumab 40 mg every other week (eow) on patient's global assessment of disease activity. The patient was to assess his/her disease activity in the past week using a visual analog scale (VAS) on a scale of 0 to 100 mm with no activity being indicated by 0 and severe activity by 100.

BASFI consist of a set of 10 questions designed to determine the degree of functional limitation in subjects with AS. The BASFI score was derived based on the average of questions 1 through 10. The first 8 questions considered activities related to functional anatomy and the final 2 questions assessed the subject's ability to cope with everyday life over the last week. A 100-mm visual analog scale (VAS) was used to answer the questions and the mean of the ten scales gave the BASFI score a value between 0 (easy) and 100 (impossible).

BASFI consisted of 10 Visual Analog Scale (VAS) questions with a response ranging from 0 (easy) to 100 (impossible). The BASFI score was derived based on the average of questions 1 through 10. A responder is a subject who demonstrates an absolute improvement of at least 10 units and a percentage improvement of at least 20% from Baseline.

Evaluation of the effect of 40 mg every other week (eow) adalimumab on Total Back Pain VAS. The subject was to assess his/her disease activity in the past week using a total spine VAS on a scale 0 (no pain) to 100 (severe pain).

Number of Subjects With a Reduction of Signs and Symptoms as Measured in Total Back Pain (an Individual Component of ASAS 20) Through Week 260 of Adalimumab Exposure [ Time Frame: Weeks 12, 24, 52, 76, 104, 128, 156, 180, 208, 220, 232, 244, and 260 ] [ Designated as safety issue: No ]

Participants assessed disease activity in the past week using a total spine VAS on a scale 0 (no pain) to 100 (severe pain). A responder is a participant who demonstrates an absolute improvement of at least 10 units and a percentage improvement of at least 20% from Baseline.

The inflammation score is the mean of the two morning stiffness-related BASDAI visual analog scale (VAS) scores (items 5 and 6 of the BASDAI): overall level of morning stiffness (0 [none] to 10 [very severe]) and duration of morning stiffness (0 [0 hours] to 10 [2 or more hours]). A decrease in inflammation represents improvement.

The inflammation score is the mean of the two morning stiffness-related BASDAI visual analog scale (VAS) scores (items 5 and 6 of the BASDAI): overall level of morning stiffness (0 [none] to 10 [very severe]) and duration of morning stiffness (0 [0 hours] to 10 [2 or more hours]). A decrease in inflammation represents improvement.

A responder is a participant who demonstrates an absolute improvement of at least 10 units and a percentage improvement of at least 20% from Baseline in inflammation (mean of the BASDAI questions 5 and 6 on scale of 0 [none] to 10 [very severe].

The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 10 (very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 (none) to 10 (very severe). Improvement in BASDAI by 20% was assessed. BASDAI Scoring:

The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 10 (very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 to 10. Improvement in BASDAI by 50% was assessed. BASDAI Scoring:

The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 10 (very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 to 10. Improvement in BASDAI by 70% was assessed. BASDAI Scoring:

Evaluation of the mean changes in CRP in subjects with adalimumab exposure from Baseline through 5 years. The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation via the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation. A decrease in CRP indicates improvement.

ASAS 40 responders - improvement of >=40% and absolute improvement of >=20 units from Baseline in a visual analog scale (VAS) for >=3 of 4 domains; Patient's Global Assessment of disease activity VAS (0 [none] to 100 [severe]); Total Back Pain VAS (0 [no pain] to 100 [severe]); BASFI VAS (0 [easy] to 100[impossible]); and Inflammation VAS (1 [none] to 10 [very severe]); and absence of any deterioration in the potential remaining domain. Applied to each scale and not to an overall global scale.

ASAS partial remission was calculated as follows: A value below 20 on a 0 - 100 point scale in each of the four domains of the ASAS (Patient's Global Assessment of Disease Activity, Pain, Function, and Inflammation). Partial remission is also regarded as a low disease activity state.

BASMI measures the range of motion based on five clinical measurements: 1) cervical rotation, 2) tragus to wall distance, 3) lumbar side flexion, 4) lumbar flexion (modified Schober's) and 5) intermalleolar distance. BASMI 0 = indicates mild disease involvement, 1 = moderate disease, and 2 = severe disease involvement. The results for cervical rotation and lumbar side flexion are the means of the left and right measurements. Scoring range 0-10. The higher the BASMI score, the more severe was the subject's limitation of movement due to their AS.

The patient is in a sitting position on the examination table with the hands on the hips. A pen mark is made at the xiphisternum and a tape measure placed around the circumference of the patient's chest at this level. The patient is asked to take a deep breath and to exhale as completely as possible while looking directly ahead. The measurement (in cm) is noted. The patient is asked to inhale as deeply as possible and the measurement (in cm) is noted. The difference in the 2 measurement points (in cm) constitutes the value for CE.

MASES is measured by scoring of entheses of 0 (no tenderness) to 3 (severe tenderness) at 13 sites on the body. The score was derived as the sum of the 13 scores divided by 3 and the total range is 0 to 13 (minimum to maximum number and severity of enthesitis).

BAS-G was measured by two VAS scores (0 to 100 mm) to reflect the effect of Ankylosing Spondylitis on subject's well-being over the past week and over the last 6 months, respectively. The average of these two scores was reported.

The subject was to assess his/her nocturnal pain intensity for the past week using a Nocturnal Pain Visual Analog Scale (Nocturnal Pain VAS). The range was 0 to 100 mm with no pain being indicated by 0 and worse possible pain by 100.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0 (no functioning) to 100 (highest level of functioning). The SF-36 Health Survey Index was completed by participants. Components of the SF-36 included the PCS and MCS, respectively. An increase in SF-36 PCS or MCS indicated improvement.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0(no functioning) to 100 (highest level of functioning).

Responders were subjects whose change in PCS score fulfilled the Minimal Clinically Important Difference (MCID). The MCID for PCS was determined by a >= 3.0 point increase during exposure to adalimumab.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0 (no functioning) to 100 (highest level of functioning). The SF-36 Health Survey Index was completed by participants. Components of the SF-36 included the PCS and MCS, respectively. An increase in SF-36 PCS or MCS indicated improvement.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0(no functioning) to 100 (highest level of functioning).

Responders were subjects whose change in MCS fulfilled the Minimal Clinically Important Difference (MCID). The MCID for MCS was determined by a >= 3.0 point increase during exposure to adalimumab.

The HUI-3 is a generic approach to the measurement of health status and assessment of health-related quality of life (HRQL). The HUI-3 classification is comprised of a total score and 8 attributes - Vision, Hearing, Speech, Ambulation, Dexterity, Emotion, Cognition and Pain. The attributes are measures on a scale from the worst score of 0 to best score of 1. The total score scale ranges from dead (= 0) and perfect health (= 1). The total score can have a negative score that is interpreted as worse than dead and the lower limit is -0.36. An increase in the HUI-3 score represents improvement.

ASQoL determined participants' quality of life and is comprised of 18 questions (yes or no) to be completed by the participant. Each statement on the ASQoL is given a score of "1" or "0." All item scores were summed to give a total score or index. Total scores ranged from 0 (good quality of life) to 18 (poor quality of life) related to ability to cope, relationships, mood, sleep, motivation, activities of everyday living, independence, and social life. Decrease in ASQoL score represents improvement.

ASQoL determined participants' quality of life and is comprised of 18 questions (yes or no) to be completed by the participant. Total scores ranged from 0 (good quality of life) to 18 (poor quality of life) related to ability to cope, relationships, mood, sleep, motivation, activities of everyday living, independence, and social life. Decrease in ASQoL score represents improvement. Responders are participants with a minimal clinically important difference (MCID) <= -1.8 points. MCID was determined by a >= 1.8 score decrease during exposure to adalimumab.

Treatment with intravenous (IV) antibiotics within 30 days of study dosing

Treatment with oral antibiotics within 14 days of study dosing

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00085644